Neuro Flashcards
What are two high yield unique characteristics for the optic nerve
1) Oligodendrocytes provide myelin for the optic nerve because it is really an extension of the brain, therefore for demyelinating diseases that target oligodendrocytes (multiple sclerosis), one of the first symptoms is visual loss.
2) Again as an extension of the brain, the optic nerve is has meninges, dura, arachnoid, pia. Therefore there is a subarachnoid space and this can be affected by intracranial pressure.
Patient presents with monocular, right nasal hemianopia. What is likely the underlying cause?
A medially expanding aneurism of internal carotid artery on the right side.
A 62 yr old woman comes to physician with decreased vision. Over the last 6 weeks she has had progressive difficulty with visualizing objects on her right side. She also has intermittent headaches that are worse in the morning. Her medical history is significant for non-small cell lung carcinoma that was diagnosed 2 years ago and treated surgically. PE shows right homonymous hemianopia. When light is shone in left eye, both pupils constrict. When light is immediately moved to right eye, her pupils appear to dilate. This patients symptoms are indicative of what
Left sided lesion of the optic tract.
This patient likely has a lesion involving the left optic tract. The optic tract contains mixed optic nerve fibers from the temporal part of the ipsilateral retina (nasal visual field) and fibers from the nasal part of the contralateral retina (temporal visual fields). Optic tract lesions consequently result in a contralateral homonymous hemianopia. The afferent limb of the pupillary light reflex involves the retina optic nerve, optic chiasm, optic tract fibers, and the pretectal nucleus in the midbrain.
pineal cyst
In most cases, a pineal cyst does not cause signs or symptoms. The majority of pineal cysts are small (roughly 80% are less than 10 mm in diameter) and asymptomatic. Symptomatic lesions are often larger (but not always), and occur most often in women in their second decade of life. Larger cysts (with a diameter >15 mm) may lead to various neurologic symptoms. Symptoms may be due to the cyst’s proximity to other structures in the brain, or hydrocephalus from compression of the cerebral aqueduct (a channel connecting the 3rd and 4th ventricles of the brain).[5]
When a pineal cyst does cause symptoms, they may include headaches (the most common symptom), hydrocephalus, disturbances in vision, and Parinaud syndrome. Although rare, people with symptomatic pineal cysts may have other symptoms such as difficulty moving (ataxia), mental and emotional disturbances, vertigo, seizures, sleep (circadian rhythm) troubles, vomiting, hormonal imbalances that may cause precocious puberty, or secondary parkinsonism.[5][6]
A 65-year-old man comes to the emergency department due to acute-onset slurred speech. He also has right-sided weakness but denies any trauma, headache, or loss of consciousness. His medical problems include hypertension and type 2 diabetes mellitus. The patient has smoked 1 pack of cigarettes daily for 20 years. Neurologic examination shows right-sided lower facial droop with sparing of the forehead muscles. Motor strength is 3/5 on the right and 5/5 on the left with a Babinski response to the right. There is also dysmetria and dysdiadochokinesia involving his right upper and lower extremities. MRI of the brain reveals an acute lacunar infarct in the brainstem, as shown in the image below. (middle cerebellar peduncle)
Which of the following cranial nerve exits the brainstem closest to the level affected by this patient’s stroke? A. Facial B. Hypoglossal C. Oculomotor D. Trigeminal E. Trochlear
Correct answer: Trigeminal
This patient has an acute lacunar ischemic stroke affecting the left medial pons at the level of the middle cerebellar peduncle. The trigeminal nerve (CN V) exits the brainstem at the lateral aspect of the mid-pons at the level of the middle cerebellar peduncles (a key neuroanatomic landmark for locating the nerve). The trigeminal sensory nuclei (eg. Principal sensory, spinal, mesencephalic) run from the midbrain to the upper cervical spine and receive afferent signals for facial sensation via all 3 branches (ophthalmic, maxillary, and mandibular). The motor nucleus is located in the lateral mid-pons and sends efferent signals to the muscles of mastication (eg temporalis, masseter, pterygoids) via the mandibular branch.
Infarct involving the anterior pons can affect corticospinal tract (contralateral hemiparesis, Babinski sign) and corticobulbar tract (contralateral lower facial palsy, dysarthria). Disruption of the corticopontine fibers that convey motor information from the cortex to ipsilateral pontine gray matter may also result in contralateral dysmetria and dysdiadochokinesia (ataxic hemiparesis). The cerebrallar deficits are contralateral to the lesion as the pontocerebellar fibers arising from the pontine gray matter decussate and enter the cerebellum through the contralateral middle cerebellar peduncle. A: facial nerve exits lower at the pontocerebellar angle; B: facial nerve exits at the medulla level; C: oculomotor nerve exits at the midbrain level ventrally; E: Trochlear nerve exits at the midbrain level dorsally.
Where is broca’s area? (relative to brain structures)
Anterior to the central sulcus
Superior to sylvian fissure
Found in inferior frontal gyrus
What is unique about conduction aphasia
It is like the opposite of global aphasia. So Wernicke and Broca are both intact so comprehension is fine, fluency is fine.
Language skills that rely on speed are fucked.
GRIEF
5 stages
other symptoms
duration
The five stages of grief per the Kübler-Ross model are denial, anger, bargaining, depression, and
acceptance, not necessarily in that order.
Other normal grief symptoms include shock, guilt, sadness, anxiety, yearning, and somatic symptoms. Simple hallucinations of the deceased person are common (eg, hearing the deceased speaking).
Duration varies widely; usually
Major depressive disorder
Diagnostic criteria
Treatment
Sleep characteristics
Episodes characterized by at least 5 of the 9 diagnostic symptoms lasting ≥ 2 weeks (symptoms must include patient- reported depressed mood or anhedonia).
Treatment: CBT and SSRIs are first line.
SNRIs, mirtazapine, bupropion can also be considered. Antidepressants are indicated if bipolar disorder is ruled out. Electroconvulsive
therapy (ECT) in select patients.
Patients with depression typically have the following changes in their sleep stages: -decreased slow-wave sleep -decreased REM latency -increased REM early in sleep cycle -increase total REM sleep -Repeated nighttime awakenings -Early-morning awakening (terminal insomnia)
Depression, often milder, lasting at least 2 years
Dysthymia aka persistent depressive disorder
Depression with atypical features
Characteristics and treatment
Characterized by mood reactivity (being able to experience improved mood in response to positive events, albeit briely), “reversed” vegetative symptoms (hypersomnia, hyperphagia), leaden
paralysis (heavy feeling in arms and legs), long-standing interpersonal rejection sensitivity.
Most common subtype of depression.
Treatment: CBT and SSRIs are first line. MAO inhibitors are effective but not first line because of their risk profile.
Bipolar disorder (1 and 2)
treatment too
Bipolar disorder (manic depression) Bipolar I defined by presence of at least 1 manic episode +/− a hypomanic or depressive episode.
Bipolar II defined by presence of a hypomanic and a depressive episode.
Patient’s mood and functioning usually return to normal between episodes. Use of antidepressants
can precipitate mania. *High suicide risk.
Treatment: mood stabilizers (eg, lithium, valproic acid,
carbamazepine, lamotrigine), atypical antipsychotics.
milder form of bipolar disorder lasting at least 2 years, fluctuating between mild depressive and hypomanic symptoms.
Cyclothymia
Onset before age 10. Severe and recurrent temper outbursts out of proportion to situation. Child is constantly angry and irritable between outbursts.
Treatment?
Disruptive mood
dysregulation
disorder
Treatment: psychostimulants, antipsychotics, CBT
Prader Willi and Angelman
Prader-Willi syndrome (PWS) –absent active
paternal gene at 15q11-13 or deletion
n Mild to moderate intellectual disability
n Hyperphagic and obese
o Angelman syndrome (AS) - 15q11q13 deletion of
maternal gene at 15q11-13
n Moderate to severe intellectual disability
n Motor delays, abnormal gait, epilepsy, paroxysmal
laughter
o PWS or AS clinical picture depends on parent
donating deleted chromosome
Fragile X
Fragile X syndrome is typically due to an expansion of the CGG triplet repeat within the Fragile X mental retardation 1 (FMR1) gene on the X chromosome.
Fragile X Syndrome (males and females)
2nd most common MR chromosomal abnormality
n Developmental delays, mild-moderate intellectual disability
n Connective tissue dysplasia
n Gaze aversion
n Macroorchidism
n Large appearing ears (not by measurement)
Characterized by poor social interactions, social communication deficits, repetitive/ritualized
behaviors, restricted interests. Must present in early childhood. May be accompanied by
intellectual disability; rarely accompanied by unusual abilities (savants). More common in boys.
Associated with increased head/brain size
Autism Spectrum Disorder
FA: Onset before age 12. Limited attention span and poor impulse control. Characterized by
hyperactivity, impulsivity, and/or inattention in multiple settings (school, home, places of worship,
etc). Normal intelligence, but commonly coexists with difficulties in school. Continues into
adulthood in as many as 50% of individuals.
Treatment?
ADHD
Treatment: stimulants (eg, methylphenidate and amphetamine) +/–
cognitive behavioral therapy (CBT); alternatives include atomoxetine, guanfacine, clonidine.
ADHD patients are not easily stimulated so they need stimulation..
Separation Anxiety Disorder & Treatment
Overwhelming fear of separation from home or attachment figure. Can be normal behavior up to
age 3–4. May lead to factitious physical complaints to avoid school.
Treatment: CBT, play therapy, family therapy
Enduring pattern of hostile, defiant behavior toward authority figures in the absence of serious
violations of social norms.
Oppositional defiant disorder
Treatment: psychotherapy such as CBT.
Repetitive and pervasive behavior violating the basic rights of others or societal norms (eg,
aggression to people and animals, destruction of property, theft). <18 yrs old, treatment?
After age 18, often reclassified as
antisocial personality disorder. Treatment for both: psychotherapy such as CBT.
What are alcohol withdrawal symptoms
Time from last drink: 3-36 hrs: minor symptoms similar to other depressants
6-48: withdrawal seizures
12-48: alcoholic hallucinosis
*peak at 36 hours
48-96 delirium tremens (DTs) in 5% of cases
Treatment: benzodiazepines
What functions are found in each part of the brain?
Frontal Parietal Temporal Occipital Cerebellum
Frontal:
- rostral: planning, problem solving, short term memory, controlling behavior
- ventral: smell
- Broca area: speech formation
- rostral the motor strip: skilled movement
- motor strip: voluntary
Parietal:
- rostral: sensory perception of self and world
- central: sensory data analyzed
Temporal:
- memory learning,
- visual
- auditory data analyzed
- Wernicke area: language interpretation
Occipital:
- vision
- visual data interpreted
Cerebellum:
- balance
- coordination
Limbic: contains the hippocampus and amygdala. Emotional processing and memory consolidation
What are the 12 cranial nerves and their functions?
- Olfactory: smell
- Optic: vision
- Oculomotor - all eye muscles except superior oblique muscle and external rectus
- Trochlear - superior oblique muscle
- Trigeminal - sensory: face, sinuses, teeth
- motor: muscles of mastication - Abducens - external rectus
- Facial - muscles of the face
- Vestibulocochlear - sensory inner ear
- Glossopharyngeal - pharyngeal musculature
Sensory: posterior part of tongue, pharynx and tonsils - Vagus - heart, lungs, bronchi, trachea, larynx, pharynx, GI tract, external ear
- Accessory - sternocleidomastoid, trapezius
- Hypoglossal - muscles of the tongue
What are the functions of astrocytes
- Form glial membrane (external limiting membrane)
- Component of blood-brain barrier
a. Control K+
b. Modulate vascular tone in the brain, controlling cerebral blood flow. - Remove
a. K+ from extracellular fluid at nodes of Ranvier during action potentials.
b. Neurotransmitters from synaptic clefts (Prevents glutamate excitotoxicity.) - Communicate through gliotransmitters (D-serine, glutamate, ATP) in response to adjacent synaptic activity.
- Produce neurotrophic factors.
- Produce scar tissue in response to CNS injury
What are satellite cells?
Satellite glial cells are the principal glial cells found in the peripheral nervous system, specifically in sensory, sympathetic, and parasympathetic ganglia. They compose the thin cellular sheaths that surround the individual neurons in these ganglia.
SGCs have been found to play a variety of roles, including control over the microenvironment of sympathetic ganglia. They are thought to have a similar role to astrocytes in the central nervous system (CNS). They supply nutrients to the surrounding neurons and also have some structural function. Satellite cells also act as protective, cushioning cells. Additionally, they express a variety of receptors that allow for a range of interactions with neuroactive chemicals.
What are the vertebrae and nerves of the spinal cord?
Vertebrae - C1-C7 *
T1-T12
L1-L5
S
Nerves, C1-C7, C8*. So the spinal nerves exit in the intervertebral foramen above the vertebraes. So C8 vertebrae does not exist but the nerve does. All the other nerves exit in a foramen below so T1-T12, L1-L5, S1-S5
The conus medullaris is around L1
Describe the spinothalamic tract
A unipolar primary sensory neuron synapses with a secondary sensory neuron in the dorsal horn. The tract neuron crosses the midline (decussation) and travels up to the brain via the anterolateral pathway aka spinothalamic and synapses at the thalamus where an interneuron that takes the signal to the primary somatosensory cortex
A major sensory tract fro the spinal cord to the cortex, crosses in the spinal cord, so the representation is in the opposite brain.
Describe the features of the brain stem
The brain stem - features long pathways, and cranial nerves instead of spinal nerves.
They are important for functions the head can do like facial expression, ingestion, respiration
–keep in mind the flexure when taking locations—
from rostral to caudal - midbrain, pons, medulla oblongata
Midbrain: cerebral peduncle
- Cranial, only 3 and 4
- visual reflexes, visual motor control
- **has dopamine projections to corticol areas significant for movement and “reward”
Pons - balloon aka “big bridge to cerebellum”
Cranial nerves - 5,6,7,8
Function - balance, sound localization, eye movement coordination
Medulla -pyramid
Cranial nerves - 9,10,11,12
Function:
-regulation of body homeostasis/heart rate, respiration, vasomotor tone, gastric secretions
-vomiting, coughing, sneezing, swallowing, gagging
Damage to medulla is death
Describe the RAS-reticular activating system
Major component: reticular formation—
Nuclei and neuronal circuits
• Net-like appearance
• Through the core of the brainstem. • Include projections to the cortex or spinal cord.
RAS - beings in the reticular formation
Rostral projections from the pons and midbrain (pontomesencephalic)
• Projection controls attention, arousal, sleep and wakefulness.
• Includes several neurotransmitters systems
Describe the corticospinal tract:
Corticospinal tract: Major motor pathway from the cortex to the spinal cord. Upper motor neuron crosses in the medulla to control contralateral muscles.
Projects to the spinal cord from the primary motor cortex as all do,
- crosses at the medulla “pyramid decussation
- travels through the lateral corticospinal tract
- synapses in the anterior horn with the lower motor neuron which synapses on skeletal muscle
Describe and distinguish between the components of the blood-CSF and blood-brain
barrier.
Blood-CSF
- choroid plexus which produces CSF and is found in all the major ventricles
- blood vessels entering the choroid plexus
- Endothelial wall of the choroidal capillaries: No barrier– are
fenestrated. - Scattered pial cells.
- Choroidal epithelial creates a blood-CSF barrier by tight junctions
– active transport, ion exchange mechanisms to determine
flow of molecules (e.g., Na+, K+, Cl-, Mg++, folates)
Blood-brain barrier
-blood vessels in subarachnoid space meeting brain tissue
-is formed by tight junctions between the brain capillary endothelial cell. Astrocyte foot processes surround the capillary but are not part of the barrier. They can control blood flow
Controls ionic environment–neurotransmission
Protects brain from toxins
Prevents drugs from entering brain Contains transporters for some critical molecules (glucose and proteins)
The blood-brain barrier may be disrupted by infections, tumors or trauma, causing
“vasogenic edema”
Explain the flow of CSF beginning from the choroid plexus to the arachnoid villae.
- Arterial blood crosses the choroid epithelium
- Lateral ventricles >
- Interventricular foramen of Monroe >
- 3rd ventricles >
- Cerebral Aqueduct >
- 4th ventricle >
- Foramen of Magendie (1 medial) and Luschka (2 lateral) >
- Subarachnoid space around brain and spinal cord
- Arachnoid granulations > venous sinuses END
Describe and give the clinical rationale for the lumbar puncture
.Lumbar puncture
L3-L4 in adults
L4-L5 in children.
Contraindicated if there is HIGH Intracranial pressure: you could create a vacuum causing brain herniation
CSF pressure: normal is <20 cm H2O in lying position
- Obtaining samples of CSF important for identifying:
- subarachnoid hemorrhage (detect blood)
- infections ex. meningitis
- Guillain Barre - an ascending weakness/paralysis commonly caused by GN Campylobacter Jejuni in which the body’s immune system attacks part of the peripheral nervous system
- MS - Introduce drugs
Identify and the meningeal layers surrounding the spinal cord and brain.
Brain:
—pachymeninges——-
Dura: 2 layers
-periosteal
-meningeal
- —leptomeninges——-
- Arachnoid - many arachnoid trabeculae and cisterns
- Pia
Spinal cord:
- 1 layer of dura mater
- Arachnoid- fewer trabeculae and 1 cistern
- Pia - forms denticulate ligaments (secures to arachnoid), filum terminale internum attaches to arachnoid, externum attaches to coccyx.)
Identify the dural folds and describe, generally, the common areas of brain herniation.
Falx cerebri - in between cerebral hemispheres (in longitudinal fissure).
Falx cerebelli - in between two
hemispheres of cerebellum.
Tentorium cerebelli - in
between the posterior
cerebral hemispheres and
the cerebellum. Wraps around the brain stem, forming a roof
Diaphragm sellae - circular
fold beneath the brain that
covers the sella turcica.
Herniation:
1- Temporal transtentorial herniation aka uncal
tentorial notch: the midbrain reticular formation goes right through the notch which is a tight space. If there is increased pressure in the supratentorial space, the brain can herniate right there, go into a coma because RAS is impinged. Tumor in temporal lobe can cause this.
- Subfalcine aka Subdural- cingulate gyrus herniates below the falx cerebri - the most common form and does not necessarily mean severe symptoms, present as headache but can progress to contralateral leg weakness.
- Central herniation or downward transtentorial: the diencephalon (thalamus and hypothalamus) and medial parts of both temporal lobes are forces through a notch in the tentorioum cerebelli.
- Cerebellar tonsillar - is a type of cerebral herniation characterised by the inferior descent of the cerebellar tonsils below the foramen magnum. (seen in chiari I malformation
Describe the locations and causes of subdural, subarachnoid and epidural hematomas.
Epidural space: Potential space between the dura and the skull
- note in the spinal cord this is a real space filled with epidural fat.
- the middle meningeal artery lies on the dura mater so tearing can cause bleeding into the epidural space.
Subdural space: Potential space between the dura and arachnoid - subdural hematoma: usually venous blood (bridging veins)
Subarachnoid space: Real space where the major arteries of the veins are found
Define fibrillation and fasciculation and explain their clinical
significance.
Electromyographic changes: fibrillations, positive sharp waves, fasciculations. These are measures of denervation.
Electromyography is an investigatory tool to assess the source muscle weakness
- Needle electrodes inserted into muscle
- Study muscle at rest (normal: no activity)
- During a contraction
Fibrillation: only detected with EMG. Short-duration, spontaneous biphasic or triphasic potentials produced by single muscle fibers. These are indicative of a denervated muscle.
These are thought to represent an unstable muscle fiber cell membrane. They both occur in peripheral nerve injuries, axonal neuropathies, motor neuron disorders and some myopathies.
Fasciculations: Larger potentials caused by spontaneous activity in a motor unit or several motor units. Caused by lower motor neuron lesions, particularly in anterior horn cell disease such as ALS. Large potentials are suggestive of denervation and reinnervation.
Describe and recognize the post-polio syndrome and its clinical
features.
.The polio virus attacks ventral horn motor neurons, causing LMN syndrome
Recovery and stable period is due to sprouting by neighboring motor neurons
So patient has period of years during which she was neurologically stable. (usually ~ 15 years) followed by progressive weakness in the same muscles originally affected.
Post-polio period occurs years later because those new sprouts cannot be sustained.
Describe the lower motor neuron syndrome and explain the
physiological basis for each of the symptoms.
The muscles that are innervated by motor neurons
- Weakness or paralysis
- Atrophy
- Muscle atrophy: Without motor neuron innervation, muscles cannot contract, so lose mass. They also lose trophic support from the motor neurons. - Hyporeflexia or areflexia
- Decreased tone (resistance to passive movement) “flaccid paresis/paralysis”
- Fibrillations, positive sharp waves or fasciculations, measured by EMG
Describe the common sites and causes of lower motor neuron
disorders.
Cell bodies in CNS (Ventral horn or brainstem nuclei)
Axons in the PNS in ventral root, spinal nerve, peripheral nerve, or cranial nerve
- Peripheral nerve, spinal nerve, or cranial nerve lesions
- Cauda equina lesions
- Strokes or tumors affecting alpha motor neurons in
ventral horn or brainstem - Polio (viral infection of α-motor neurons)
- Amyotrophic lateral sclerosis ( “ALS” or “motor neuron
disease” that also affects upper motor neurons) - Guillain-Barré (demyelinating disease)
- Werdnig-Hoffman disease (degeneration of anterior horn)
Describe the innervation of clinically important dermatomes. C2 C5 C6 C7 T10 L4 L5 S1
C2-back of head
C5-shoulder, lateral arm
C6-digits 1-2, lateral forearm
C7-digit 3
T10-umbilicus (belly butten)
L4-knee, and medial lower leg
(down on ALL 4’s)
L5-dorsal foot, big toe
S1-lateral foot, small toe, So1e
Describe the blood supply to the spinal cord
Anterior spinal artery
(1) located in the ventral median fissure
- Supplies anterior 2/3 of spinal cord
Posterior spinal artery
(2) located in the posterolateral sulci Supplies posterior 1/3 of spinal cord
Vasocorona: a series of branches from the anterior and posterior spinal arteries that form a crown (“corona”) around the cord.
Anterior and posterior radicular arteries arise from segmental arteries at each spinal
level to serve their respective roots and ganglia.
• The anterior and posterior spinal medullary arteries arise at intermittent levels to
augment the blood supply.
• The great Artery of Adamkiewicz is unusually large anterior radicular artery arising on
the left from T9-L1. It supplies the majority of the lumbar and sacral SC.
Great radicular artery of adamkiewicz is so important that it is thought to supply the whole bottom of the spinal cord and blockage presents as a lower spinal cord injury
What is the T4-T9 watershed area?
T4-T9 watershed area
• Fracture dislocations of vertebra can interfere with blood supply. • Arterial disease can obstruct great radicular artery. • Occlusion of aorta during surgery can produce ischemic damage to blood supply.
Its a region between the endpoints of the thoracic radicular artery
& great radicular artery of adamkiewicz
Drop in blood pressure, can lead to this watershed region being necrotic.
Describe spinal cord Lower motor neurons with important functions
C3-C5 Motor neurons to the Phrenic nerve controlling diaphragm.
S3-S4 Onuf’s nucleus: Motor neurons innervating urethral and external anal sphincter which enable voluntary control of urination and defecation.
S2-S4 Motor neurons to pelvic floor muscles.
*very low spinal cord lesions (cauda equina) can produce bowel and bladder incontinence
What is an acoustic neuroma?
An acoustic neuroma is a noncancerous growth that develops on the eighth cranial nerve. Also known as the vestibulocochlear nerve, it connects the inner ear with the brain and has two different parts. One part is involved in transmitting sound; the other helps send balance information from the inner ear to the brain.
Describe the series of events in an neuron action potential
- Enough graded potentials activate voltage gated sodium channels (-50mV)
- Sodium influxes, the neuron depolarizes significantly.
- Then the sodium channels close and potassium channels open, hyperpolarizing until the voltage gated potassium channels close.
- inactivated sodium channels are no longer inactive.
With all the exocytosis at the nerve terminal, wouldn’t the membrane be huge?
There is a process of endocytosis to remove membrane from the nerve terminal.
Adaptor proteins connect clathrin to vesicular membrane forming clathrin coated pits.
Clathrin assemble into coat, curving membrane.
Dynamin ring comes and pinches off membrane.
Coated vesicle is then moved away from terminal along the actin filament
Hsc70/Auxillin - remove the clathrin. Can start storing NT again
Glutamate
The major excitatory neurotransmitter in the CNS • Contained in approximately 50% of all neurons, and virtually all
excitatory neurons.
• Post-synaptic receptor type:
Metabotropic: May be excitatory or inhibitory, depending on the state of
the neuron.
• Ionotropic: NMDA (N-methyl-D-aspartate), kainate and AMPA. **All
excitatory
NMDA is both a voltage-gated and ligand-gated Ca2+ ion channel • The receptor is blocked by Mg2+ at resting membrane potential
• Uses the AMPA receptor and influx of Na+ to depolarize the membrane
to remove the Mg2+ block
It is both a voltage-gated and ligand-gated Ca2+ ion channel • The receptor is blocked by Mg2+ at resting membrane potential
• Uses the AMPA receptor and influx of Na+ to depolarize the membrane
to remove the Mg2+ block
NMDA activation in the presence of depolarization, enables
Ca2+ to enter cell.
• Increased intracellular [Ca2+ ] can activate calcium-dependent
signaling cascades.
• Intracellular signals can produce long-term synaptic changes
that are important for
• development of synapses • regulating neural circuits • learning and memory (Long-term potentiation; LTP)
• Long-term changes include changes in dendritic spines and
insertion of AMPA receptors: Increased responsiveness of post-synaptic neurons after repeated stimulation of neurons (e.g., in hippocampus).
Glutamate excitotoxicity:
Trauma and disease that impair ATP-generation can cause
increased glutamate release or decreased glutamate reuptake.
• Glutamate NMDA channels allow Ca2+ to leak into cells.
• Increased Ca2+ causes increased water uptake and stimulation of
intracellular enzymes that degrade proteins, lipids, and nucleic acids
• Examples of conditions thought to be associated with
glutamate toxicity: ALS, Alzheimer’s, tumors, oxygen
deficiency, ischemia, trauma, repeated seizures.
GABA
Major inhibitory neurotransmitter of the CNS • Contained in about 30% of CNS neurons
- Post-synaptic receptor type:
- Ionotropic: GABAa receptor, GABA gated Cl-channel
- Metabotropic: GABAb functionally linked to potassium or calcium ion channels
Dopamine
3 pathways
Mesolimbic pathway: -Reward pathway (addiction)
- Schizophrenia
- Depression
Nigrostriatal Pathway: Control of movement
-Parkinson’s disease
Mesocortical pathway:
Working memory
Schizophrenia
ADHD
Involved in reward-motivated
behavior and motor pathways
CNS- Neurons originate in
brainstem regions (ventral
tegmental area and substanstia
nigra) 46
Drugs that influence dopamine transmission: • Anti-psychotics (-) • Nicotine, cocaine,
methamphetamine (+) • Amphetamines (Adderall) (+) • Methylphenidate (Ritalin) (+)
Acetylcholine
Main neurotransmitter in the PNS and ANS, but also has
neuromodulator functions in CNS
• PNS- Neuromuscular junctions
• ANS- sympathetic (pre-) & parasympathetic (pre- & post-
ganglionic) neurons
• CNS- Neurons originate in the basal forebrain (nucleus basalis)
and the brainstem (dorsolateral midbrain-pons) and have
widespread connections to the cortex
- Involved in arousal, attention, memory and motivation • Nucleus basalis degenerates in Alzheimer’s disease
- Associated with memory loss, personality change and dementia
Drugs that influence ACh transmission in the CNS: • Nicotine (on nictotinic
receptors) (+) • Atropine (-) • Scopolamine (-)
Describe the general rules for herniated discs and the nerves they impinge
So in the cervical vertebrae, because the corresponding nerve exits above the vertebrae, a C5-C6 herniated disc impinges on C6 nerve.
In the lumbar its the same but for a different region. The interventricular foramen is large so the corresponding spinal nerve exits above the disc.
So an L4-L5 herniation will not impinge onf the L4 nerve but rather the L5 as it is traveling in the cauda equina. Impinging the L5 nerve.
Terms for weakness, the 4 P’s
Paralysis: weakness so severe that a
muscle cannot be contracted.
• Paresis: weakness, or partial paralysis.
• Plegia: severe weakness or paralysis.
– e.g., Diplegia refers to bilateral lower limb
weakness. Quadriplegia to all 4 limbs. – Hemiplegia refers to one side of the body
weakness (arm and leg)
• Palsy: imprecise term for either weakness
or no movement.
Explain the scoring for muscle strength.
Interpret the scoring for spinal cord stretch reflexes
.0/5 No contraction
1/5 Muscle flicker, no movement
2/5 Movement, but not against gravity 3/5 Movement against gravity, but not against resistance
4/5 Movement against some resistance 5/5 Normal
0+ absent 1+ trace 2+ normal 3+ brisk 4+ non-sustained clonus 5+ sustained clonus 1-3 can look normal so always refer to opposite side for asymmetry or even with upper and lower
Describe the receptor, circuit and functions of the stretch reflex, golgi-tendon
reflex and flexor withdrawal reflexes.
Stretch reflex - 1. Muscle stretch receptor excited (connected to Ia afferent) 2. Ia afferent makes an excitatory synapse onto quadriceps motor neurons,
causing muscle contraction
3. Ia afferent also makes an excitatory synapse onto an inhibitory interneuron,
which inhibits hamstring (flexor) motor neurons
(L3,L4)
Golgi tendon reflex
Stimulus: Muscle tension Circuit: GTO > lb > lb inhibitory interneuron > motor neuron to homonymous muscle
(also excites antagonist muscles)
Flexor withdrawal - stimulated leg flexes to withdraw after cutaneous receptor activated > cutaneous afferent fiber from nociceptor alpha, < activates interneurons which inhibit the extensors and activate flexor in pained foot > for opposite foot the opposite happens, extensor activated, flexor inhibited to stand
What are the stretch reflexes at these levels
L3-L4
C5-C6 (2)
C7-8
S1
L3-4 – patella (3,4 kick down the door)
C5-6 – biceps
C5-6 – brachioradialis
(5,6 pick up sticks)
C7-8– triceps
(7-8 keep it straight)
S1 – Achilles
(1,2 buckle my shoe)
What are the muscle spindles and the system?
Proprioceptors: providing information about body position/movement.
-Arranged in parallel with skeletal muscles fibers.
• Intrafusal muscle fibers within a
connective tissue capsule.
• Attached to skeletal
muscle fibers.
Muscle spindle contains this lil capsule, which has efferent (gamma) and afferent nerves. It has two types of sensory nerves, group Ia which responds to rapid, dynamic stretch and
group II which responds to sustained, tonic stretch
Gamma motor neuron: γ-motor neurons are motor neurons that only innervate muscle spindle intrafusal fibers. • DO NOT cause skeletal muscle
fibers to contract. • Increase the excitability of the
muscle spindle.
Normally both alpha- and gamma-
motor neurons are CO-activated. • Gamma activity increases during
skilled movements and motor
learning.
So stretch is going to have a greater response with gamma neuron activity and also picks up slack if muscles are contracted
Describe the functions of the corticospinal, corticobulbar and reticulospinal tract pathways.
Describe the functions of the corticospinal, corticobulbar and reticulospinal tract pathways.
Corticospinal tract:
The corticospinal tract is the primary pathway for goal-directed movements.
• Only descending pathway to
project directly to α-motor
neurons of distal muscles.
• It is the only pathway that
generates fine movements of
the fingers.
The corticospinal tract originates in the primary motor cortex as well as the premotor and somatosensory cortex.
*Large Betz Cells in motor cortex (layer 5) project directly to motor neurons
Reticulospinal tracts project mainly ipsilaterally (some bilateral) to medial α-motor neurons throughout the length of the spinal cord. They contribute to posture and gait-related movements.
Generate feedforward preparatory muscle activation. •Contribute to muscle tone.
Corticobulbar
The corticobulbar tract is a descending pathway responsible for innervating several cranial nerves, and runs in paralell with the corticospinal tract
Origin
- Motor cortex (precentral gyrus and anterior part of the paracentral lobule)
Course / Path - The corticobulbar tracts leave the internal capsule and enter the basilar part of the pons as numerous bundles [1] The fibres leave the cerebral crus adjacent to the corticospinal tract.[1] The fibres can take several paths and have several different terminations:
i) Termine directly on alpha motor neurones or interneurones innervating alpha motorneurons in the brainstem. These control somatic motor acitivity in the head e.g. muscles that control mastication, expression and eye movement.
ii) Axons that innervate motor nerve cranial nuclei can decussate (cross) before they terminate, resulting in them innervating contralateral muscles. As some decussate and some descend ipsilaterally, it results in bilateral descending control. [2]
iii) Directly innervate cranial nerves or through interneurones I.E. via the corticospinal tract. [2]
Function
- Innervates muscles of the face, tongue, jaw, and pharynx, via the cranial nerves.[3]
- The corticobulbar tract directly innervates the nuclei for cranial nerves:
V - Trigeminal- muscles for mastication
VII- Facial- muscles of the face
XI- Accessory- sternocleidomastoid and trapezius
XII- Hypoglossal- muscles of the tongue [4]
- Cranial nerves motor regions of X (vagus nerve) in the nucleus ambiguus.[4]
Describe the motor deficits that would follow specific upper motor neuron
lesions of the cortex or spinal cord.
- Generally, the corticospinal tract
- Trauma to lateral primary motor cortex (face and arm)
- Trauma to internal capsule
- What lesions could cause unilateral leg weakness or paralysis? (3) possibilities
Lesions above the spinal cord produce contralateral deficits. Lesions of the spinal cord produce symptoms on the same side of the lesion
Deficits are always below the level of the lesion
________________________________
Corticospinal Tract:
Major deficits with CST lesions: •Voluntary motor weakness (distal > proximal) on one side of the body. •Babinski sign
______________________________
Trauma to lateral primary motor cortex
1. Weakness in right arm and low face 2. UMN (lower face, entire arm).
3. Pathways are CBT and CST
aka. Contralateral Unilateral face and hand hemiparesis.
________________________________
Trauma to internal capsule
Pure motor hemiparesis with lesion in internal capsule- starting with the lower face.
_________________________________
Trauma to motor cortex (contralateral)
•A lesion affecting the ipsilateral spinal cord—UMN signs
•Peripheral nerve–LMN signs
Define the basic morphology and function of the receptors and axons that mediate cutaneous sensation, proprioception, temperature and pain sensation.
Cutaneous (AlphaBeta)
-Meissner corpuscle: surface, motion in dermis
-Merkel cell:
detects edges, indentations, slowly adapting
- Ruffini corpuscle - skin stretch, aligned parallel with stretch lines
- Pacinian corpuscle: deep and with onion like layers, vibration
Proprioception: (1a, II) - the largest, most myelin, fastest
- muscle spindle
- GTO
Temperature (Alphadelta, C)
Pain (Alphadelta, C)
Describe the pathway of peripheral sensitization
The interaction of nociceptors with the “inflammatory soup” of substances to decrease threshold of activation for nociceptors
Prostaglandins: •Increase response of nociceptive fibers.
These nociceptors release substance P which causes vasodilation but also mast cell degranulation releasing histamine as a positive feedback cycle since histamine also activates nociceptors.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. aspirin and ibuprofen): •Inhibit cyclooxygenase (COX) to prevent synthesis of prostaglandins
Describe the pathway of central sensitization
An immediate, activity dependent increase in the excitability of neurons in
the dorsal horn of the spinal cord following high levels of activity in the
nociceptive afferents to increase pain sensitivity.
Mechanisms of central sensitization
- Transcription independent (windup) lasts only during stimulation = acute.
- Transcription dependent (allodynia) outlast stimulus for hours and can be
mediated by COX = chronic.
• Development of or increase in spontaneous activity
• Reduction in threshold for activation by peripheral stimuli
• Expansion of receptive field size (conversion of nociceptive-specific
neurons to wide dynamic neurons that now respond to both innocuous
and noxious stimuli)
-the glutamate channel is open, with repeated stimuli you unblock the NMDA receptor which initiaties a signal cascade. With repeated stimulation, with alot of NT, gene expression changes which permanently changes the neuron
Lateral and medial vestibulospinal tracts
elaborate sensory system in the inner ear with specialized receptors that monitor head position, movement and acceleration.
Lateral vestibulospinal (balance): projects to the entire spinal cord. It projects **ipsilaterally to medial LMNs to proximal muscles. Especially facilitates extensor muscles in response to deviations from stable balance and upright balance.
Medial vestibulospinal (positioning of head and neck): projects on to cervical.Projects BILAterally to control head position in response to acceleration "vestibulocervical reflex
important in reflex excitability
**Tectospinal tract
orienting movements of the head to visual or auditory stimuli. It also helps to coordinate the eyes and head.
“whats that?!”
Originates in the superior colliculus and crosses in the MIDBRAIN (not just the one of the only ones to cross in the midbrain but out of the brain stem pathways, the only one to cross at all! ) (tecto and rubro)
Is in the medial motor system.
Generates orienting movements of the head to visual or auditory stimuli. It also helps to coordinate the eyes and head.
Rubrospinal tract
Originates in the red nucleus of the midbrain.
Crosses in the midbrain
Travels next to LCST in the spinal cord
Only extends to the *cervical spinal cord
Facilitates FLEXOR muscles>extensors
* this is important because its where a decerebrate - lesion below the midbrain - cause ALL LIMBS to extend vs decorticate which has flexion of the arms.
ONLY pathway that travels and projects lateral!
Lateral: only the LCST and rubrospinal
Which UMN tracts are uncrossed?
- anterior corticospinal tract
- Reticulospinal tract
- Lateral vestibulospinal tract
- Medial vestibulospinal tract
- Corticobulbar
Which UMN tracts terminate bilaterally
- anterior corticospinal tract
- Reticulospinal tract
- Medial vestibulospinal tract (cervical only)
- Most of corticobulbar
A 70 year-old right-handed person presented with progressive gait instability and some “trouble looking upwards.” He had a tendency to lose his balance when walking. He was an avid birdwatcher and indicated that every day he would go out and “look up into the trees at the birds.”
The patient stated “I had more trouble over the past couple of years because I couldn’t look up without bending my whole neck back.”
Diagnosis: upward gaze paresis
Limb ataxia
MRI showed a pineal cyst compressing nerves responsible for eye movement and motor movement.
In most cases, a pineal cyst does not cause signs or symptoms. The majority of pineal cysts are small (roughly 80% are less than 10 mm in diameter) and asymptomatic. Symptomatic lesions are often larger (but not always), and occur most often in women in their second decade of life. Larger cysts (with a diameter >15 mm) may lead to various neurologic symptoms. Symptoms may be due to the cyst’s proximity to other structures in the brain, or hydrocephalus from compression of the cerebral aqueduct (a channel connecting the 3rd and 4th ventricles of the brain).[5]
When a pineal cyst does cause symptoms, they may include headaches (the most common symptom), hydrocephalus, disturbances in vision, and Parinaud syndrome. Although rare, people with symptomatic pineal cysts may have other symptoms such as difficulty moving (ataxia), mental and emotional disturbances, vertigo, seizures, sleep (circadian rhythm) troubles, vomiting, hormonal imbalances that may cause precocious puberty, or secondary parkinsonism.
A 34-year old cardiothoracic surgeon developed left neck and shoulder pain, with numbness and tingling radiating down the ulnar aspect of his arm into the 4th and 5th fingers. On exam, he had some weakness of the intrinsic muscles of the left hand and decreased sensation to pinprick and light touch over the left fourth and fifth digits. The remainder of the exam was normal.
You had pain, but also decrease in sensation. Think of dermatome map and that points you to C8. What about ulnar nerve.
The left neck pain lets you know it is up near the vertebral column.
The motor, weakness of intrinsic muscles of hand.
Most likely is herniation between C7 and T1 impinging on C8.
